Bakker T R, Renno T, Jongeneel C V
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Switzerland.
J Immunol. 1999 Mar 15;162(6):3456-62.
We introduce a new experimental system combining adenovirus-mediated gene transfer and fetal thymic organ culture (FTOC). This system allowed us to efficiently express in developing thymocytes a mutant form of the NF-kappa B inhibitor I kappa B alpha (mut-I kappa B) and to study the maturation defects occurring when NF-kappa B activation is inhibited during fetal development. Fetal thymocytes infected with adenovirus containing mut-I kappa B were found to develop normally until the CD44-CD25+, CD4-CD8- double-negative stage, while production of more mature double-positive and single-positive populations was strongly decreased. Proliferation, as measured by the percentage of cells in cycle appeared normal, as did rearrangement and expression of the TCR beta-chain. However, apoptosis was much higher in FTOC infected with adenovirus containing mut-I kappa B than in FTOC infected with a control virus. Taken together, these results suggest that NF-kappa B plays a crucial role in ensuring the differentiation and survival of thymocytes in the early stages of their development.
我们引入了一种新的实验系统，该系统结合了腺病毒介导的基因转移和胎儿胸腺器官培养（FTOC）。这个系统使我们能够在发育中的胸腺细胞中高效表达核因子κB抑制剂IκBα的突变形式（mut-IκB），并研究在胎儿发育过程中抑制核因子κB激活时出现的成熟缺陷。发现感染含有mut-IκB的腺病毒的胎儿胸腺细胞在CD44-CD25 +、CD4-CD8-双阴性阶段之前正常发育，而更成熟的双阳性和单阳性群体的产生则大幅减少。通过细胞周期中细胞百分比衡量的增殖似乎正常，TCRβ链的重排和表达也是如此。然而，感染含有mut-IκB的腺病毒的FTOC中的细胞凋亡比感染对照病毒的FTOC中的细胞凋亡要高得多。综上所述，这些结果表明核因子κB在确保胸腺细胞发育早期的分化和存活中起着关键作用。
